Alzheimer's disease and small vessel disease differentially affect white matter microstructure

Mostra el registre complet Registre parcial de l'ítem

  • dc.contributor.author Tranfa, Mario
  • dc.contributor.author Gispert López, Juan Domingo
  • dc.contributor.author Barkhof, Frederik
  • dc.date.accessioned 2025-02-18T06:18:21Z
  • dc.date.available 2025-02-18T06:18:21Z
  • dc.date.issued 2024
  • dc.description.abstract Objective: Alzheimer's disease (AD) and cerebral small vessel disease (cSVD), the two most common causes of dementia, are characterized by white matter (WM) alterations diverging from the physiological changes occurring in healthy aging. Diffusion tensor imaging (DTI) is a valuable tool to quantify WM integrity non-invasively and identify the determinants of such alterations. Here, we investigated main effects and interactions of AD pathology, APOE-ε4, cSVD, and cardiovascular risk on spatial patterns of WM alterations in non-demented older adults. Methods: Within the prospective European Prevention of Alzheimer's Dementia study, we selected 606 participants (64.9 ± 7.2 years, 376 females) with baseline cerebrospinal fluid samples of amyloid β1-42 and p-Tau181 and MRI scans, including DTI scans. Longitudinal scans (mean follow-up time = 1.3 ± 0.5 years) were obtained in a subset (n = 223). WM integrity was assessed by extracting fractional anisotropy and mean diffusivity in relevant tracts. To identify the determinants of WM disruption, we performed a multimodel inference to identify the best linear mixed-effects model for each tract. Results: AD pathology, APOE-ε4, cSVD burden, and cardiovascular risk were all associated with WM integrity within several tracts. While limbic tracts were mainly impacted by AD pathology and APOE-ε4, commissural, associative, and projection tract integrity was more related to cSVD burden and cardiovascular risk. AD pathology and cSVD did not show any significant interaction effect. Interpretation: Our results suggest that AD pathology and cSVD exert independent and spatially different effects on WM microstructure, supporting the role of DTI in disease monitoring and suggesting independent targets for preventive medicine approaches.
  • dc.description.sponsorship We thank the study participants. EPAD is supported by the EU/EFPIA Innovative Medicines Initiative (IMI) grant agreement 115736. The project leading to this paper has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 115952. This Joint Undertaking receives the support from the European Union's Horizon 2020 research and innovation program and EFPIA. This communication reflects the views of the authors and neither IMI nor the European Union and EFPIA are liable for any use that may be made of the information contained herein.
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Tranfa M, Lorenzini L, Collij LE, Vállez García D, Ingala S, Pontillo G, et al. Alzheimer's disease and small vessel disease differentially affect white matter microstructure. Ann Clin Transl Neurol. 2024 Jun;11(6):1541-56. DOI: 10.1002/acn3.52071
  • dc.identifier.doi http://dx.doi.org/10.1002/acn3.52071
  • dc.identifier.issn 2328-9503
  • dc.identifier.uri http://hdl.handle.net/10230/69628
  • dc.language.iso eng
  • dc.publisher Wiley
  • dc.relation.ispartof Ann Clin Transl Neurol. 2024 Jun;11(6):1541-56
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/115952
  • dc.rights © 2024 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0/
  • dc.subject.other Alzheimer, Malaltia d'
  • dc.title Alzheimer's disease and small vessel disease differentially affect white matter microstructure
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

Col·leccions

Articles (Hospital del Mar Research Institute)
Articles (Departament de Medicina i Ciències de la Vida)
Documents OpenAIRE (Open Access Infrastructure for Research in Europe)